Role of Vascular Endothelial Growth Factor in Non-Small Cell Lung Cancer Pathogenesis

Abstract

The angiogenesis is an important process in the pathogenesis of malignancies. It is regulated by various growth factors, with the vascular endothelial growth factor (VEGF) playing the central role. The aim of the present study was to evaluate possible associations of functional VEGF −2578C>A, −634G>C, and +936C>T polymorphisms with the risk for occurrence and progression of non-small cell lung cancer (NSCLC) in patients living in Republic of Belarus. Materials and Methods: A total of 202 patients (147 males and 55 females) diagnosed as having the NSCLC. The control group consisted of 336 individuals (245 males and 91 females) without an oncopathology. The total DNA was isolated from peripheral blood. We investigated the single nucleotide polymorphisms of VEGF (rs 2010963), (rs 699947), (rs 3025039). The genotyping was performed by PCR-RFLP analysis. Results: Our results revealed a marginally significant association of the –2578CC genotype (p=0.002) with a greater degree of tumor spread (Т2–Т4). Heterozygous genotypes –2578СА and +936СT carriers were included into the follow-up group significantly more often (р=0.021 and р=0.012, respectively). Our study demonstrate that VEGF –2578A/C and +936C/T polymorphisms are among the factors determining the individual peculiarities of NSCLC course in this population and can be used for clarifying the prognosis of the disease.

Investigation the Association of the VEGFR-2 and -2578C\A Polymorphism as a Risk Factor for Incidence of Lung Cancer in Babylon Province

“…High VEGF expression is associated with tumor growth and metastatic process, while the inhibited VEGF expression results in suppressed growth of cancer [24]. Several functional polymorphisms of the VEGF gene that may affect serum VEGF expression level, included −634G\C, −1154G\A, 936C\T, −1498C\ T, −2578C\A, and −460C\T [25] .The −2578C/A of VEGF gene, have been demonstrated to modulate the levels of VEGF expression in tumor growth especially with lung cancer [26] .Recently, the effects of the VEGF gene polymorphism on the Lung cancer risk have been extensively studied; however, the results of these studies were conflicting and ambiguous.The findings of our study proposed that VEGF -2578C\A variant significantly increased the risk of Lung cancer.These results indicate that relative risk of lung cancer associated with −2578C/A of the VEGFgene lung carcinoma in their patients.The present results agreement with [27][28][29], all of which demonstrated a high significant correlation of the-2578C\A VEGF with lung carcinomas, and not agreement with Liu C et al 2015 and Yang F et al 2018 [30] these studies were conducted on Asians, Caucasians and Indians it did not show a significant association of the -2578C\A VEGF gene and lung cancer.In conclusion, our result showed no significant correlation with regards to levels of VEGFR-2 in lung cancer patients while showed a significant associations of VEGF -2578C\ A polymorphism with LC susceptibility in Babylon population. VEGF -2578C\A in over dominant model significantly increases the risk of Lung cancer and can be useful as predisposing genetic marker for LC.…”

Relationship between vascular endothelial growth factor -2578C > a gene polymorphism and lung cancer risk: a meta-analysis

“…A total of 14 studie s [14][15][16][17][18][19][20][21][22][23][24][25][26][27] on the association between VEGF -2578C > A gene polymorphism and the susceptibility of lung cancer, were included into this metaanalysis (Table 1 and Fig. 1).…”

Association between IL18-607C/A and -137G/C polymorphisms and susceptibility to non-small cell lung cancer in a Chinese population

“…Moreover, certain hereditary factors are involved in its pathogenesis. Such factors include the genes that encode XPA-binding protein 2, vascular endothelial growth factor, stromal-derived factor-1, tankyrase 1, epidermal growth factor, TNF-related apoptosis-inducing ligand, and chemokine (C-C motif) ligand 2 (Krupnova et al, 2015;Luo et al, 2015;Masroor et al, 2015;Pei et al, 2015;Wang et al, 2015;Xu et al, 2015;Li et al, 2016b).…”